NM_203454.3:c.812T>C

Variant names:

• chr1-183647970-A-G
• rs1174658
• NM_203454.3:c.812T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203454.3(APOBEC4):​c.812T>C​(p.Phe271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,898 control chromosomes in the GnomAD database, including 126,235 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12212 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114023 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 32 publications found

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2375584E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	NM_203454.3	MANE Select	c.812T>C	p.Phe271Ser	missense	Exon 2 of 2	NP_982279.1
	RGL1	NM_015149.6		c.-33+11469A>G		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11469A>G		intron	N/A	NP_001284598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	ENST00000308641.6	TSL:1 MANE Select	c.812T>C	p.Phe271Ser	missense	Exon 2 of 2	ENSP00000310622.4
	RGL1	ENST00000304685.8	TSL:1	c.-33+11469A>G		intron	N/A	ENSP00000303192.3
	APOBEC4	ENST00000481562.1	TSL:3	n.246-173T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60336 AN: 151926 Hom.: 12193 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.363 AC: 91333 AN: 251408 AF XY: 0.362

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.391 AC: 572193 AN: 1461854 Hom.: 114023 Cov.: 65 AF XY: 0.389 AC XY: 282871 AN XY: 727228

African (AFR) AF: 0.481 AC: 16105 AN: 33478

American (AMR) AF: 0.304 AC: 13602 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9586 AN: 26136

East Asian (EAS) AF: 0.185 AC: 7364 AN: 39700

South Asian (SAS) AF: 0.329 AC: 28347 AN: 86258

European-Finnish (FIN) AF: 0.362 AC: 19344 AN: 53420

Middle Eastern (MID) AF: 0.449 AC: 2590 AN: 5768

European-Non Finnish (NFE) AF: 0.406 AC: 451515 AN: 1111978

Other (OTH) AF: 0.393 AC: 23740 AN: 60392

GnomAD4 genome AF: 0.397 AC: 60395 AN: 152044 Hom.: 12212 Cov.: 32 AF XY: 0.392 AC XY: 29136 AN XY: 74300

African (AFR) AF: 0.471 AC: 19510 AN: 41462

American (AMR) AF: 0.337 AC: 5148 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1103 AN: 5180

South Asian (SAS) AF: 0.315 AC: 1522 AN: 4828

European-Finnish (FIN) AF: 0.362 AC: 3823 AN: 10562

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26885 AN: 67958

Other (OTH) AF: 0.376 AC: 792 AN: 2108

Alfa AF: 0.394 Hom.: 32278

Bravo AF: 0.400

TwinsUK AF: 0.408 AC: 1514

ALSPAC AF: 0.426 AC: 1643

ESP6500AA AF: 0.469 AC: 2068

ESP6500EA AF: 0.395 AC: 3401

ExAC AF: 0.368 AC: 44661

Asia WGS AF: 0.274 AC: 955 AN: 3478

EpiCase AF: 0.397

EpiControl AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.53
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.2	N
PhyloP100		1.7
PrimateAI	Benign	0.29	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.087
Sift	Benign	0.76	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.19
ClinPred		0.0059	T
GERP RS		4.5
Varity_R		0.054
gMVP		0.16
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1174658; hg19: chr1-183617105; COSMIC: COSV58017675;